John Fox's side were unbeaten heading into the game with the 4-2 Colts, who had broken the Seattle Seahawks' unbeaten run in their last game at Lucas Oil Stadium.
That proved to be the case again as they became the first team to defeat the 2013 Broncos as Andrew Luck threw for three touchdown passes in a 39-33 victory for his side in a game where turnovers were crucial.
Read how all the action unfolded in our commentary below.
1.04amWe are in store for an excellent game this morning as Peyton Manning returns to the team he spent 15 seasons with for the first time as a Bronco. He comes up against his replacement, 2012 first overall pick Andrew Luck.
1.06amManning had such a distinguished career with the Colts as he guided them to the playoffs 11 times during his spell with the club, winning the Super Bowl once in the 2006 season. He also won the AFC Championship in that 06 season as well as in 2009.
1.08amThe 37-year-old also broke the NFL touchdown record during his spell in Indy when he threw for 49 touchdowns in the 2004 season, which was only broken by Tom Brady in the 2007 season by one score.
1.10amManning returns to the stadium they call, 'The place that Peyton built', off the back of his success at the club where he turned them from perennial strugglers into Super Bowl contenders year in, year out.
1.11amThe Broncos come into Lucas Oil Stadium unbeaten this season thanks to their high-powered offense led by Manning who has thrown for 22 touchdowns in just six games. They're leading the NFL in scoring by a considerable distance and are on pace to break the record for the amount of points scored held by the New England Patriots in 2007.
1.13amManning has spread his passes around this season as Wes Welker leads the team with eight touchdowns while tight end Julius Thomas is second with seven, while Demaryius Thomas and Eric Decker have four and two respectively.
1.15amThe Denver defense hasn't been great this season but they're boosted by the return of Champ Bailey and more importantly All-Pro linebacker Von Miller. Miller had over 18 sacks last season and will provide the Broncos with ability to get to the passer that they so desperately need. They have allowed the most passing yards by any team this season.
1.16amThe Colts will look to take advantage of that tonight with Andrew Luck who has proven in his 22 games in the NFL that he is more than capable of filling the void left by Manning. He had a huge win over the Seattle Seahawks last time out in Lucas Oil Stadium and he will hope to end another team's unbeaten run in this game.
1.18amDefensively the Colts were suspect in their defeat to the San Diego Chargers on Monday night. They will need Robert Mathis to get to Manning in this game to boost his 9.5 sack total along with their other defensive lineman.
1.20amThere has been a war of words so to speak between Colts owner Jim Irsay and former general manager Bill Polian about the Manning era at Indianapolis. Irsay claimed that the team moved on from the All-Pro to win more Super Bowls after winning just once in 15 year with Manning at the controls. Manning was too classy to fire back but that didn't stop his head coach John Foxfiring back at Irsay while Polian was also furious with his former boss.
1.22amThere might be a bit of awkward moment between Manning and Irsay when the meet in a pre-game ceremony to honour the 37-year-old for his work at the Colts.
1.25amJust to spice the game up a little bit more, the Colts have opened the roof on Lucas Oil Stadium a known annoyance of Manning. The mind games have well and truly been stepped up for this game.
1.29amThe Colts are almost injury free bar the loss of pass rusher Bjoern Werner who has been out for the past few weeks with a foot injury.
1.30amHowever, the Broncos come into this game without some key players. Wesley Woodyard, their captain and signal caller on defense is out with an injury, while cornerbacks Tony Carter and Quentin Jammer are also out. Offensive lineman Orlando Franklin is also missing, which could affect Manning's protection in this game.
Q1 15:00Luck will begin at the 21 following Vaughn's kick return.
Q1 13:22The Colts get away with an apparent fumble from Trent Richardson on second down but don't make the yardage on third down with another run from the back and are forced to punt.
Q1 12:59McAfee punts the ball to only the 40 where Manning will begin against his old club.
Q1 12:22The Broncos go three and out as Moreno can't get the first down on a third down carry needing only a yard after ripping off nine on his first run. Butler did well on second to break up a pass for Welker.
Q1 11:29Colquitt punts for the first time of the night and his kick is downed inside the Colts' 20 at their seven, where Luck will begin again.
Q1 11:17Luck gets his side moving immediately as he finds Wayne on a slant route for 15 yards as he beats Bailey in coverage. A battle between two great veterans there.
Q1 9:15SACK! A big sack of Luck brings the Colts' drive to a halt as he is brought down for an eight-yard loss on second down by Phillips. They got some yardage back on a penalty on Phillips on the next play but Luck's third down pass to Hilton is broken up forcing a punt from McAfee.
Q1 8:59McAfee's punt is returned to the Denver 44 by Holliday for 12 yards.
Q1 8:55Manning fires deep down the right-hand sideline for Decker who makes the catch beating Toler in coverage to move his side to the 15 for a 17-yard pick up. A good throw and route by the quarterback and receiver.
Q1 8:22The Broncos take the lead as Manning fires to Decker for a 15-yard touchdown on an out route as he managed to shake off the coverage of Bethea in the corner of the endzone. It's that easy for the Broncos this season.
Q1 8:22Vaughn returns the ball to the 26 where Luck will begin.
Q1 7:55Luck gets his side moving on a play-action pass as he rolls out to the right and fires a strike across his body to Hilton for a 19-yard pick up.
Q1 6:49The Colts keep moving as Luck hits Heyward-Bey for seven yards and then fires to Wayne on a crossing route for 14 yards to shift them to the Denver 34.
Q1 5:54Heyward-Bay secure another big grab as Luck hits him down the seam on a go route on third down and 10 for a 27-yard strike to move his side to the Denver seven-yard line.
Q1 4:09Luck can't get the ball into the endzone on three attempts as the Denver defense holds firm, with good coverage and a decent pass rush. Vinatieri will kick a 27-yard field goal.
Q1 4:05Vinatieri boots the ball through the posts to get his side on the board.
Q1 4:00Holliday returns the ball to the Denver 13 where Manning will begin again.
Q1 3:20The Broncos go three and out again as Moreno is stopped just short of the marker and it's fourth and inches. After he picked up nine on first down again and Manning's pass on second fell incomplete. Colquitt's punt is caught by Hilton at the 35 and he takes it back to the 39.
Q1 2:11The Colts go three and out as a costly false start penalty give it first and 15 and they can't get the yardage back through the arm of Luck while Richardson is stacked up on the ground.
Q1 1:27Holliday collects McAfee's punt and runs it back but is stripped of the ball as he goes out of bounds. The ball lands in bounds and is collected by Brown who runs the ball in for the touchdown. It is not ruled a touchdown but the Colts will have the ball on the Denver 11. Madness!
Q1 1:20The Colts take the lead as Luck fools the Denver defense with a play-action pass and fires a swing pass to Heyward-Bey who has the open field to run into and he runs in for the score from 11 yards.
Q1 1:12Holliday gets a great return on the kickoff from McAfee as he gets the ball to the halfway line before he's dropped by the kicker.
Q1 1:04The Broncos get a first down as Butler is penalised for defensive holding on Welker to move them into Colts territory.
Q1 0:00Another third and one situation for the Broncos when the second quarter resumes as they get nine yards on first and second from two runs from Moreno.
Q1 0:00END OF FIRST QUARTER: Denver Broncos 7-10 Indianapolis Colts
Q2 14:30Manning fires on play-action to Tamme who picks up the first down with a seven-yard catch down the right-hand sideline.
Q2 13:30Manning keeps his side moving as he fires the ball to Decker down the left-hand sideline for 13 yards to move his team into the redzone.
Q2 11:56The Broncos regain the lead as Manning fires down the seam for his tight end Julius Thomas who makes a fingertip grab and taps his feet down in the endzone to complete the score over Bethea. That was a 12-yard strike by Manning for his 24th touchdown of the season.
Q2 11:50Vaughn returns the ball to the 26 where Luck will begin again.
Q2 10:02The Colts drive comes to an immediate end as they get stopped on second and third down trying to run the ball with Brown and Richardson needing only a yard but Miller makes the tackle to stop them in their tracks.
Q2 9:33Denver will start at their 6 after a penalty was called on Caldwell for holding.
Q2 9:06Manning is sacked by Mathis who comes round on his blindside and strips the ball from his hand. The ball lands in the endzone and is recovered by Francois. The officials rule a two-point safety but this could be a touchdown as he looked to have gathered the ball in bounds.
Q2 8:46The safety is confirmed, which forces the Broncos to punt away and Brazill takes the ball to the 34.
Q2 8:19Luck fires the ball to his running back Brown who peels off on a wheel route down the left-hand sideline and he takes the ball to the Denver 34 for a 28-yard game.
Q2 6:50Luck runs for the first down himself as he jukes two tackles and gets the 11 yards much to the disbelief of the Broncos defense.
Q2 5:50The Colts regain the lead as Luck fires to his full-back Havili, who he brought up to the line and he back beats Ayers in a foot face to cross the endzone for a 20-yard touchdown. Havili is having a big night as he made the play to strip Holliday of the ball earlier.
Q2 5:08The Broncos' offense is struggling at the minute as they go three and out as Manning's pass to Demaryius Thomas is dropped by the reciever, which would have been enough for the first down. Colquitt's punt is taken to the Indy 43 by Vaughn.
Q2 4:04The Colts go three and out as they can't make the Broncos' offense pay for their miscues as Heyward-Bey drops Luck's pass, which would have been a certain touchdown under pressure from Rodgers-Cromartie. Luck's pass on third down was dangerous and was nearly picked off. McAfee's punt was downed at the Denver two-yard line where Manning will begin.
Q2 2:00Denver get a huge third down conversion on their own two-yard line as Manning fakes to Moreno and fires a wide receiver screen to Demaryius Thomas and he finds a hole and runs to the 20 for a 16-yard pick up.
Q2 1:44Denver's offense continues to struggle as they can't move the ball as Manning throws three straight incompletions two to Demaryius Thomas and one to Decker. Hilton collects Colquitt's punt and takes it to the 50.
Q2 1:06Luck finds the first down immediately and he throws to Browns on screen pass to move his side into Broncos territory after finding Heyward-Bey on first for four yards.
Q2 0:32Luck drives his team to the redzone as he connects with his tight end Fleener over the middle evading the rush of the Broncos defensive ends.
Q2 0:10Luck strikes for a huge score for the Colts as he finds Fleener again on an out pattern with a quick throw and the tight end runs into the endzone beating the challenge of Moore for the eight-yard score.
Q2 0:00HALF-TIME: Denver Broncos 14-26 Indianapolis Colts
3.15amThe Colts lead at the break with Luck beating the old maestro Manning at his own game with a crucial score just before the half. The Denver offense has looked out of sync so far in this game bar their brief moments in the redzone, they will need to get their act into gear if they want to remain unbeaten.
3.16amThe Colts' defense have done a good job of stopping Moreno in the ground game and have also shut down Welker and Demaryius Thomas in the passing game so far, which no team in the league has been able to do. They face a massive challenge to keep it up though.
3.18amDenver's porous pass defense has continued to struggle despite the addition of Miller. They've allowed 199 yards to Luck in the first half and three touchdowns. They'll need to stop him if they're to get back into the game.
Q3 15:00Manning will start from the 20 as McAfee's kick goes out of the endzone.
Q3 13:35The Broncos get off to a bad start as they're forced to punt as Manning's deep pass to Decker on third down falls incomplete after the offensive line gave away a holding penalty setting them back to first and 20. Colquitt's punt is caught at the 30 by Hilton for the fair catch.
Q3 12:23The Colts can't take advantage of Denver's continued struggles as Luck's pass to Heyward-Bey for nine yards on third down, when they needed 12 for the first down. McAfee's punt is collected at the Denver 16 by Holliday for the fair catch.
Q3 11:06Things aren't going well for Manning in this game at all as his pass to Moreno on a wheel route falls incomplete after they could only get two yards on first and second down. Colquitt's punt is caught at the Indy 29 by Hilton. It's a punting contest at the moment.
Q3 9:38Richardson finally gets something going on the ground for the Colts as he gets a first down on a third down and two over the left guard, where he found a big enough hole to get six yards.
Q3 8:17Rodgers-Cromartie saves seven points for the Broncos as he makes a crucial pass break up to stop Hilton catching a bomb down the seam from Luck, which would have been a sure touchdown if not for the cornerback. That could be huge in this game.
Q3 8:10Holliday fumbles the punt for the second time of the night but he manages to jump on it just in time before Brown could pounce on it. Lucky escape for Holliday.
Q3 7:40Manning and co's struggles continue as they can't get the first down as his screen pass to Moreno on third down is snuffed out by Landry, who drops the back for only a four-yard gain when they needed six for the pickup. A penalty on Colquitt's punt moves the Colts to the Denver 44.
Q3 6:01A first down at last as Luck fires over the middle to Wayne who makes an excellent grab, as he goes up high to get the ball and bring it down under pressure. A penalty on Vickerson for knocking the helmet off Richardson adds 15 yards to the play to move the Colts to the Denver 15.
Q3 5:00The Colts extend their advantage as Luck goes in for the score himself with a brilliant run to the outside and he coasts into the endzone for the 10-yard score with the aid of a block from Wayne.
Q3 4:23Manning makes a good throw under pressure and Welker makes an excellent catch with the ball inches off the ground to pick up a first down with a 16-yard reception bouncing back from taking a huge sack from Mathis on first down.
Q3 3:55The Broncos get a huge break with a pass interference penalty on Vaughn for 22 yards and then with the next play inside Colts territory Hillman runs for 14 yards as he gashes the defense on the left-hand side.
Q3 2:27Two more first downs for the Broncos as Manning fires to Demaryius Thomas and then Welker to get the yardage to move their side to the Colts' 11.
Q3 0:47The Broncos fail to get the ball into the endzone as they commit two costly penalties to back themselves up 10 yards and Manning't throw into the endzone falls incomplete leaving Prater with a 31-yard field goal.
Q4 12:31Manning goes deep downfield looking for Decker and he manages to find him and somehow avoids getting intercepted as Vaughn tips the ball up to the receiver and he makes the grab moving his team to the Colts' 31.
Q4 12:11Manning evades the rush from the Colts' defense and manages to step up in the pocket and throw to Demaryius Thomas on a deep post route and he makes the catch low in the endzone for a 31-yard score as Landry took a bad angle on the play.
Q4 12:11The Broncos go for two on the conversion and Manning's throw is dropped by Julius Thomas, so it's just the six for John Fox's side.
Q4 12:11Luck will begin at the 20 as Prater's kick sails out of the endzone.
Q4 8:49Moreno powers into the endzone from one-yard out right through the middle of the line and all of a sudden we have a game on here. How crucial will that fumble from Richardson be?
Q4 8:49Luck will begin at the 20, a score here is crucial for the Colts.
Q4 8:40The Colts get a first down straightaway as Lenon is penalised for a hold on Brown.
Q4 7:21A huge moment in the game as the Colts fail on third down as Luck misses a wide open Wayne, and even worse for Pagano's side is that the receiver goes down clutching his knee. He would have been in for a touchdown had the throw been on him rather than at his feet.
Q4 7:15McAfee's punt is caught by Holliday at the Denver 15 for the fair catch.
Q4 6:59Walden gets to Manning on the right-hand side of the line and hits his arm as he throws, the ball bobbles in the air and lands straight in the arms of Angerer, who makes the interception at the Denver 20.
Q4 6:02The Colts can't punch the ball into the endzone as Heyward-Bey makes a crucial drop on second down, which would have been enough for the first down. That forces Vinatieri into a 42-yard field goal.
Q4 6:02Vinatieri knocks his kick through the posts to make it a nine-point game.
Q4 5:57Holliday takes the ball out of the endzone on the kickoff but is forced out at the 15.
Q4 4:55Welker gets his team out of a huge hole on third and 17 with a magnificent catch after Manning took a sack on first down. That catch was almost identical to the one he dropped in Super Bowl 46 for the Patriots.
Q4 3:22Welker moves his side to the one-yard line with two more receptions of 13 and 25 yards as he beats the coverage of Butler.
Q4 3:10Hillman fumbles the ball goalline and the Colts manage to recover it. That is huge! A score would have put the Broncos right in the game with a huge momentum swing.
Q4 2:55Vickerson costs the Broncos big again as he runs straight into Luck following an incompletion and is called for roughing the passer, which gets the Colts off their goalline and hands them another set of downs on their 20.
Q4 2:00The Colts just run the clock down with the ball into the two-minute warning as Brown just runs into his own line. The Broncos need two scores to get back into the game.
Q4 1:42The Colts are committing several penalties on their punt. This could be a tactic to wind the clock down further. They've already taken 18 seconds off the clock.
Q4 0:00FULL-TIME: Denver Broncos 33-39 Indianapolis Colts
5.20amThe Broncos sustain their first loss of the season at the hands of the Colts, as Manning falls to defeat against his replacement in Indianapolis.
5.22amPagano's side knocked Manning's offense out of their rhythm for the majority of the game until they backed off with their pressure late in the match and it almost cost them but a couple of late turnovers helped the secure the victory.
5.25amThe Broncos now drop to 6-1 and second place in the AFC West behind the 7-0 Kansas City Chiefs, who are now the only unbeaten team in the NFL this season. The Colts meanwhile stretch their lead at the top of the AFC South to two games over the Tennessee Titans and three over the Houston Texans.
5.27amThanks for joining our commentary this evening. We'll be back tomorrow with all the action from Monday Night Football, until then, goodbye.